Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Metabolic landscape of human alveolar type II epithelial cells undergoing epithelial-mesenchymal transition induced directly by silica exposure.

Epithelial-mesenchymal transition (EMT) plays an irreplaceable role in the development of silicosis. However, molecular mechanisms of EMT induced by silica exposure still remain to be addressed. Herein, metabolic profiles of human alveolar type II epithelial cells (A549 cells) exposed directly to silica were characterized using non-targeted metabolomic approaches. A total of 84 differential metabolites (DMs) were identified in silica-treated A549 cells undergoing EMT, which were mainly enriched in metabolisms of amino acids (e.g., glutamate, alanine, aspartate), purine metabolism, glycolysis, etc. The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica. Remarkably, glutamine catabolism was significantly promoted in the silica-treated A549 cells, and the levels of related metabolites (e.g., succinate) and enzymes (e.g., α-ketoglutarate (α-KG) dehydrogenase) were substantially up-regulated, with a preference to α-KG pathway. Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail (zinc finger transcription factor). Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

Photoresponsive Hydrogel Dressing Containing Nanoparticles with Excellent Synergetic Photodynamic, Photothermal, and Chemodynamic Therapies for Effective Infected Wound Healing.

Bacterial resistance to antibiotics can negatively affect the treatment of infected skin wounds. The combination of synergistic antibacterial therapies with photodynamic, photothermal, and chemodynamic therapies has been recognized as one of the most promising approaches. In this study, we have developed MSN@Ce6@MnO2-CS/Ag (MCMA) nanoparticles to serve as powerful antibacterial agents when exposed to both 660 nm visible light and 808 nm near-infrared (NIR) light. Through dual-light irradiation, MCMA can induce hyperthermia and generate reactive oxygen species (ROS), leading to a remarkable enhancement in photothermal antibacterial effects and accelerating wound healing. It has a peroxidase-like catalytic activity and promotes the generation of hydroxyl radicals (·OH) by catalyzing the decomposition of H2O2. In vitro antibacterial experiments demonstrated the excellent antibacterial activity of MCMA. The antibacterial efficacy of MCMA at a concentration of 250 µg ml-1 was found to be 99.6 and 100% toward Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, respectively, under irradiation with an 808 and 660 nm laser. The results of the animal experiments demonstrated that MCMA can effectively accelerate wound healing through wound ulceration inhabitation. These findings substantiate the assertion that synthetic MCMA represents an efficacious strategy for bacterial inhibition and wound healing.

NIR-activatable nitric oxide generator based on nanoparticles loaded small-molecule photosensitizers for synergetic photodynamic/gas therapy.

BACKGROUND: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. RESULTS: Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. CONCLUSIONS: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.

Use of pumice stone and silica fume as precursor material for the design of a geopolymer.

Background: Geopolymers are alternative materials to cement because they require less energy in their production process; hence, they contribute to the reduction in CO 2 emissions. This study aims to evaluate the possibility of using industrial residues such as silica fume (SF) to improve the physical and mechanical properties of a pumice stone (PS)-based geopolymer. Methods: Through an experimental methodology, the process starts with the extraction, grinding, and sieving of the raw material to carry out the physical and chemical characterization of the resulting material, followed by the dosage of the geopolymer mixture considering the factors that influence the resistance mechanical strength. Finally, the physical and mechanical properties of the geopolymer were characterized. This research was carried out in four stages: characterization of the pumice stone, design of the geopolymer through laboratory tests, application according to the dosage of the concrete, and analysis of the data through a multi-criteria analysis. Results: It was determined that the optimal percentage of SF replacement is 10%, which to improves the properties of the geopolymer allowing to reach a maximum resistance to compression and flexion of 14.10 MPa and 4.78 MPa respectively, showing that there is a direct relationship between the percentage of SF and the resistance. Conclusions: Geopolymer preparation involves the use of PS powder with a composition rich in silicon and aluminum. The factors influencing strength include the ratio of sodium silicate to sodium hydroxide, water content, temperature, curing time, molarity of sodium hydroxide, and binder ratio. The results showed an increase in the compression and flexural strength with 10% SF replacement. The geopolymer's maximum compressive strength indicates its non-structural use, but it can be improved by reducing the PS powder size.

Recombinant Esterase (BaCEm) Immobilized on Polyethyleneimine-Impregnated Mesoporous Silica SBA-15 Exhibits Outstanding Catalytic Performance.

A recombinant esterase, BaCEm, derived from Bacillus aryabhattai and heterologously expressed in Escherichia coli, was successfully immobilized on polyethyleneimine-impregnated mesoporous silica SBA-15. This immobilization utilized glutaraldehyde as a crosslinker. Optimal conditions were established with a PEI/SBA-15 ratio of 25% (w/w), a pH of 7.5, and a glutaraldehyde concentration of 0.5% (w/w), resulting in a loading capacity of 76.4 mg/g, a recovery activity of 43.5%, and a specific activity of 7917 U/g for BaCEm. The immobilized BaCEm demonstrated high enantioselectivity, with an "E" value of 203.92, in the resolution assay of (R,S)-ethyl indoline-2-carboxylate. Notably, the immobilized enzyme, compared to its free counterpart, exhibited enhanced thermostability, maintaining 95.4% of its activity after 3 h at 30 °C. It also showed significant tolerance to organic solvents, retaining 48.4% and 28.7% residual activity in 10% v/v acetonitrile and acetone, respectively. Moreover, its storage stability was confirmed, with 68.5% residual activity preserved after 30 days at 4 °C. Remarkably, the immobilized BaCEm retained 58.1% of its activity after 10 reuse cycles, underscoring the potential of polyethyleneimine-impregnated mesoporous silica SBA-15 as an effective support for enzyme immobilization, promising for industrial applications.

Advances in Nanotherapy for Targeting Senescent Cells.

Aging is an inevitable process in the human body, and cellular senescence refers to irreversible cell cycle arrest caused by external aging-promoting mechanisms. Moreover, as age increases, the accumulation of senescent cells limits both the health of the body and lifespan and even accelerates the occurrence and progression of age-related diseases. Therefore, it is crucial to delay the periodic irreversible arrest and continuous accumulation of senescent cells to address the issue of aging. The fundamental solution is targeted therapy focused on eliminating senescent cells or reducing the senescence-associated secretory phenotype. Over the past few decades, the remarkable development of nanomaterials has revolutionized clinical drug delivery pathways. Their unique optical, magnetic, and electrical properties effectively compensate for the shortcomings of traditional drugs, such as low stability and short half-life, thereby maximizing the bioavailability and minimizing the toxicity of drug delivery. This article provides an overview of how nanomedicine systems control drug release and achieve effective diagnosis. By presenting and analyzing recent advances in nanotherapy for targeting senescent cells, the underlying mechanisms of nanomedicine for senolytic and senomorphic therapy are clarified, providing great potential for targeting senescent cells.

Silica 3D printed scaffolds as pH stimuli-responsive drug release platform.

Silica-based scaffolds are promising in Tissue Engineering by enabling personalized scaffolds, boosting exceptional bioactivity and osteogenic characteristics. Moreover, silica materials are highly tunable, allowing for controlled drug release to enhance tissue regeneration. In this study, we developed a 3D printable silica material with controlled mesoporosity, achieved through the sol-gel reaction of tetraethyl orthosilicate (TEOS) at mild temperatures with the addition of different calcium concentrations. The resultant silica inks exhibited high printability and shape fidelity, while maintaining bioactivity and biocompatibility. Notably, the increased mesopore size enhanced the incorporation and release of large molecules, using cytochrome C as a drug model. Due to the varying surface charge of silica depending on the pH, a pH-dependent control release was obtained between pH 2.5 and 7.5, with maximum release in acidic conditions. Therefore, silica with controlled mesoporosity could be 3D printed, acting as a pH stimuli responsive platform with therapeutic potential.

Performance studies of an ultrafast gamma Cherenkov imaging Screen based on Silica fibers array.

High-energy gamma rays produced in inertial confinement fusion (ICF) experiments are crucial for studying implosion dynamics. These gamma rays, characterized by their extremely short durations, represent the least disturbed products of fusion, preserving vital birth information. To detect such γ-rays, ultrafast radiation detectors with high time resolution are necessary. This study introduces a newly developed Cherenkov optical image screen designed for ultra-fast gamma-ray imaging. Composed of pure quartz fiber material, the imaging screen features a single fiber pixel size of 0.6 mm and a thickness of 3 cm. Theoretical investigations explore the luminous time response and efficiency of the Cherenkov optical imaging screen under gamma-ray irradiation. Experimental validation was conducted using a steady-state gamma-ray source with an average energy of 1.25 MeV. Results demonstrate that the image screen achieves a spatial resolution limit of 0.75 mm. The temporal response exhibits a full width at half maximum of less than 0.4 ns when excited by a high-energy electron beam with a single pulse duration of several picoseconds.

One-pot synthesis and covalent conjugation of methylene blue in mesoporous silica nanoparticles - A platform for enhanced photodynamic therapy.

Photodynamic therapy (PDT) is an emerging clinical modality for diverse disease conditions, including cancer. This technique involves, the generation of cytotoxic reactive oxygen species by a photosensitizer in the presence of light and oxygen. Methylene blue (MB) is a cationic dye with an ability to act as photosensitizing and bioimaging agent. The direct utilization of MB as photosensitizer for biological applications has often been impeded by its poor photostability and unwanted tissue interactions. Nanocarriers such as mesoporous silica nanoparticles (MSNs) provide an effective means of overcoming these limitations. However, the mere physical adsorption of the dye within the MSN can result in leakage, compromising the effectiveness of PDT. Therefore, in this work, we report the conjugation of MB into MSNs using novel MB-silane derivatives, namely MBS1 and MBS2, to create dye-doped and amine-functionalized MSNs (MBS1-AMSN and MBS2-AMSN). The PDT efficacy and bioimaging capability of these nanoparticles were compared with those of MSNs in which MB was non-covalently encapsulated (MB@AMSN). The synthesized nanoparticles, ultra-small in size (≤ 35 ± 4 nm) with monodispersity, exhibited enhanced fluorescence quantum yields. MBS1-AMSN demonstrated 70-fold increase, while MBS2-AMSN showed 33-fold improvement in fluorescence quantum yields compared to MB@AMSN at the same concentration. Covalent conjugation resulted in a 2-fold enhancement in the singlet oxygen quantum yield of the dye in MBS1-AMSN and 1.2-fold improvement in MBS2-AMSN, compared to non-covalent encapsulation. Assessment on RAW 264.7 macrophages revealed superior fluorescence in cell imaging for MBS1-AMSN, establishing it as a more efficient PDT agent compared to MBS2-AMSN and MB@AMSN. These findings suggest that MBS1-AMSN holds significant potential as a theranostic nanoplatform for image-guided PDT.

Novel sampling and gas-phase derivatization strategy: Proof-of-concept by profiling ionic polar metabolites using gas chromatography-mass spectrometry.

Metabolomic research involves the comprehensive analysis of metabolites in biological samples and has many applications. Gas chromatography-mass spectrometry (GC-MS) is an established and widely used approach for metabolic profiling. However, sample preparation and metabolite derivatization are time-consuming, and derivatization options are limited. We propose gas-solid phase derivatization (GSPD) as a novel sampling and derivatization method that uses a silica monolith substrate and gaseous derivatization reagents for metabolomics using GC-MS. We developed a method to measure the organic acids and sugar phosphates responsible for glycolysis and the tricarboxylic acid (TCA) cycle. GSPD simplifies the sample preparation and can be applied to derivatization reactions that are difficult to perform in solution owing to solvent limitations. The developed method was applied to human plasma and tomato pulp and was shown to have a higher detection performance than the conventional method. This study provides a strategy to simplify sample preparation and expand derivatization options for GC-MS-based metabolomics.

Geology, mineralogy, geochemistry and genesis of volcano-sedimentary hosted Lake Abiyata diatomite in central main Ethiopian Rift.

The Abiyata Diatomite deposit is located in the Main Ethiopian Rift, which is characterized by strong extensional tectonics. The deposit is mostly made up of diatomaceous earth, which is a sedimentary rock made up of the fossilized remnants of diatoms, which are tiny algae. Diatomite's geological, geochemical, and mineralogical features, as well as its formation, are discussed in this research. To characterize diatomite from Abiyata, chemical, mineralogical, technological, and micro paleontological examinations were conducted on samples collected from outcrops and stream sections. The XRD characteristic peaks of diatomite demonstrate that it is primarily made up of Opal A silica, however certain crystalline phases were discovered in adequate amounts. Quartz and feldspar were the predominant crystalline phases, with lesser amounts of Calcite, Cristobalite, Illite, Mordinite, Wairakite, Halloysite, Clinoaptilolite, Adularia, and Tridymite. From SEM photomicrographs diatomites are primarily formed of benthic freshwater diatom species such as Staurosirella pinnata, Staurosira construens, Pseudostaurosira brevistriata, Epithemia Sorex and surirella pinnata. Diatom species, sedimentary profile sections and mineralogical data suggest that diatomite was deposited in lacustrine-type freshwater shallow lake environment. Chemical data obtained from 10 diatomite samples show that while silica is the bodybuilding material for diatomite. i.e., Silica (SiO2), 76.9 %; Alumina (Al2O3), 3.49 %; Sodium Oxide (Na2O), 1.52 %; Potassium Oxide (K2O), 1.107 %; Iron Oxide (Fe2O3), 1.1 %; Loss on ignition (LOI) 13.7 and other oxides are below 1 %. Studies from technological properties like physical tests, chemistry, and mineralogy and micropaleontology of Abiyata diatomite suggest that calcined diatomite can be used for waste treatment processes in the filter aid industry and as filler material.

Soft and Deformable Thermoresponsive Hollow Rod-Shaped Microgels.

Depending on their aspect ratio, rod-shaped particles exhibit a much richer 2D and 3D phase behavior than their spherical counterparts, with additional nematic and smectic phases accompanied by defined orientational ordering. While the phase diagram of colloidal hard rods is extensively explored, little is known about the influence of softness in such systems, partly due to the absence of appropriate model systems. Additionally, investigating higher volume fractions for long rods is usually complicated because non-equilibrium dynamical arrest is likely to precede the formation of more defined states. This has motivated us to develop micrometric rod-like microgels with limited sedimentation that can respond to temperature and reversibly reorganize into defined phases via annealing and seeding procedures. A detailed procedure is presented for synthesizing rod-shaped hollow poly(N-isopropylacrylamide) microgels using micrometric silica rods as sacrificial templates. Their morphological characterization is conducted through a combination of microscopy and light scattering techniques, evidencing the unconstrained swelling of rod-shaped hollow microgels compared to core-shell microgel rods. Different aspects of their assembly in dispersion and at interfaces are further tested to illustrate the opportunities and challenges offered by such systems that combine softness, anisotropy, and thermoresponsivity.

Amorphous silica nanoparticles exhibit antitumor activity in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is mainly treated with cytotoxic chemotherapy. However, this treatment is not always effective, and an important percentage of patients develop recurrence. Nanomaterials are emerging as alternative treatment options for various diseases, including cancer. This work reports the synthesis, characterization, antitumor activity evaluation, and sub-acute toxicity studies of two formulations based on amorphous silica nanoparticles (SiNPs). They are functionalized with 3-aminopropyltriethoxisilane (Si@NH2) and folic acid (FA; Si@FA). The results show that SiNPs reduce the viability and migration of TNBC MDA-MB-231 and 4T1 cell lines and Si@FA do not affect the growth of the mammary nonmalignant HC11 cells. In addition, Si@FA induces reactive oxygen species (ROS) generation and displays antiproliferative and subsequently proapoptotic effects in MDA-MB-231 cells. Moreover, none of the SiNPs cause signs of sub-acute toxicity in mice when administered at 30 mg/kg over a month. In conclusion, these nanosystems display intrinsic antitumor activity without causing toxic in vivo effects, being a promising therapeutic alternative for TNBC.

Developing Method for Minor Acidic O-Glycan Analysis in Mucin and Cancer Cell Samples.

Minor acidic glycans, such as sulfated and phosphorylated glycans, constitute only a small fraction of biological glycome, making their analysis a considerable challenge. In this study, we developed a technique to analyze minor acidic O-glycans in biological samples. First, efficient reaction conditions for the release of O-glycans from the proteins were determined. Next, a high-throughput method was established for the recovery of minor acidic glycans using NH2 spin columns. The performance of the established method was evaluated using mucin samples, and sulfated O-glycans were successfully detected in bovine submaxillary gland mucin and porcine stomach mucin. We also analyzed the minor acidic O-glycans in cultured cancer cells. In addition to trifucosylated sulfated O-glycans and disulfated O-glycans, sulfated O-glycans with KDN were detected in LS174T cells. The relative amount of sulfated glycans in LS174T cells was almost 10-fold higher than that in the other cells. Moreover, a large polylactosamine-type sulfated O-glycan with a molecular weight >3500 was detected in MKN45 cells. Interestingly, phosphorylated ribose, possibly bound to serine/threonine, was observed in all the cells used in this study. Thus, our established analytical method allows for the analysis of minor acidic O-glycans that cannot be detected using existing glycomics methods.

Preparation of DNA nanoflower-modified capillary silica monoliths for chiral separation.

Innovative chiral capillary silica monoliths (CSMs) were developed based on DNA nanoflowers (DNFs). Baseline separation of enantiomers such as atenolol, tyrosine, histidine, and nefopam was achieved by using DNF-modified CSMs, and the obtained resolution value was higher than 1.78. To further explore the effect of DNFs on enantioseparation, different types of chiral columns including DNA strand containing the complementary sequence of the template (DCT)-modified CSMs, DNF2-modified CSMs, and DNF3-modified CSMs were prepared as well. It was observed that DNF-modified CSMs displayed better chiral separation ability compared with DCT-based columns. The intra-day and inter-day repeatability of model analytes' retention time and resolution kept desirable relative standard deviation values of less than 8.28%. DNF2/DNF3-modified CSMs were able to achieve baseline separation of atenolol, propranolol, 2'-deoxyadenosine, and nefopam enantiomers. Molecular docking simulations were performed to investigate enantioselectivity mechanisms of DNA sequences for enantiomers. To indicate the successful construction of DNFs and DNF-modified CSMs, various charaterization approaches including scanning electron microscopy, agarose gel electrophoresis, dynamic light scattering analysis, electroosmotic flow, and Fourier-transform infrared spectroscopy were utilized. Moreover, the enantioseparation performance of DNF-modified CSMs was characterized in terms of sample volume, applied voltage, and buffer concentration. This work paves the way to applying DNF-based capillary electrochromatography microsystems for chiral separation.

Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/ß-catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over-activated Wnt pathway, while Wnt16-deficient mice has a more severe Knee OA. However, the efficacy of direct intra-TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small-molecule drugs such as Wnt16 usually exhibit short-lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double-layer slow-release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro-cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over-activation of the Wnt/ß-catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA.

From cane to nano: advanced nanomaterials derived from sugarcane products with insights into their synthesis and applications.

Sugarcane-based products are inherently rich in elements such as silicon, carbon and nitrogen. As such, these become ideal precursors for utilization in a wide array of application fields. One of the appealing areas is to transform them into nanomaterials of high interest that can be employed in several prominent applications. Among nanomaterials, sugarcane products based on silica nanoparticles (SNPs), carbon dots (CDs), metal/metal oxide-based NPs, nanocellulose, cellulose nanofibers (CNFs), and nano biochar are becoming increasingly reported. Through manipulation of the experimental conditions and choosing suitable starting precursors and elements, it is possible to devise these nanomaterials with highly desired properties suited for specific applications. The current review presents the findings from the recent literature wherein an effort has been made to convey new development in the field of sugarcane-based products for the synthesis of the above-mentioned nanomaterials. Various nanomaterials were systematically discussed in terms of their synthesis and application perspectives. Wherever possible, a comparative analysis was carried out to highlight the potential of sugarcane products for the intended purpose as compared to other biomass-based materials. This review is expected to stand out in delivering an up-to-date survey of the literature and provide readers with necessary directions for future research.

This review focuses on sugarcane-derived nanomaterials such as silica, nano cellulose, nanofibers, nanocrystals and metal/nonmetal nanoparticles and their application in various energy and environmental fields.

Glycolytic reprogramming governs crystalline silica-induced pyroptosis and inflammation through promoting lactylation modification.

Prolonged inhalation of environmental crystalline silica (CS) can cause silicosis, characterized by persistent pulmonary inflammation and irreversible fibrosis, but the mechanism has not been elucidated. To uncover the role and underlying mechanism of glycolytic reprogramming in CS-induced pulmonary inflammation, the mouse silicosis models and glycolysis inhibition models were established in vivo. And the CS-induced macrophage activation models were utilized to further explore the underlying mechanism in vitro. The results showed that CS induced lung inflammation accompanied by glycolytic reprogramming and pyroptosis. The application of glycolysis inhibitor (2-DG) suppressed CS-induced pyroptosis and alleviated lung inflammation. In vitro, 2-DG effectively impeded CS-induced macrophage pyroptosis and inflammatory response. Mechanistically, 2-DG suppressed pyroptosis by inhibiting NLRP3 inflammasome activation both in vivo and in vitro. Furtherly, metabolite lactate facilitated NLRP3-dependent pyroptosis synergistically with CS particles, while blocking the source of lactate largely alleviated NLRP3 inflammasome activation and subsequent pyroptosis triggered by CS. More profoundly, the increment of lactate induced by CS might drive NLRP3-dependent pyroptosis by increasing histone lactylation levels. In conclusion, our findings demonstrated inhibiting glycolytic reprogramming could alleviate CS-induced inflammatory response through suppressing NLRP3 -dependent pyroptosis. Increased glycolytic metabolite lactate and protein lactylation modifications might represent significant mechanisms during CS-induced NLRP3 activation and macrophage pyroptosis.

Silica-induced ROS in alveolar macrophages and its role on the formation of pulmonary fibrosis via polarizing macrophages into M2 phenotype: a review.

Alveolar macrophages (AMs), the first line against the invasion of foreign invaders, play a predominant role in the pathogenesis of silicosis. Studies have shown that inhaled silica dust is recognized and engulfed by AMs, resulting in the production of large amounts of silica-induced reactive oxygen species (ROS), including particle-derived ROS and macrophage-derived ROS. These ROS change the microenvironment of the AMs where the macrophage phenotype is stimulated to swift from M0 to M1 and/or M2, and ultimately emerge as the M2 phenotype to trigger silicosis. This is a complex process accompanied by various molecular biological events. Unfortunately, the detailed processes and mechanisms have not been systematically described. In this review, we first systematically introduce the process of ROS induced by silica in AMs. Then, describe the role and molecular mechanism of M2-type macrophage polarization caused by silica-induced ROS. Finally, we review the mechanism of pulmonary fibrosis induced by M2 polarized AMs. We conclude that silica-induced ROS initiate the fibrotic process of silicosis by inducing macrophage into M2 phenotype, and that targeted intervention of silica-induced ROS in AMs can reprogram the macrophage polarization and ameliorate the pathogenesis of silicosis.